In vitro and in vivo studies of intracellular and extracellular electrophysiology in hippocampus suggest that the role of opioid substances in this structure is a highly strategic one, in that a small number of opiate receptors and enkephalinergic pathways exert a powerful influence on the excitability of a large proportion of pyramidal and granule cells. This laboratory was among the first to demonstrate the excitatory influence of opiates in the CAl field of hippocampus. We have subsequently reported that opiates (morphine) and opioid peptide analogs produced differential effects on intracellular recordings of CAl cells depending upon the region of the cell to which the opiate is applied (basal dendrites and somal region vs apical dendrites). Additionally, it was shown that inhibitory influences appear to be enhanced in the CAl region of tolerant rats. These findings indicate a selective role for opiates as disinhibitory in the hippocampus. In addition to the above CAl influences, we have shown recently that opiates and opioid peptides enhance the transmission of sensory information into the dentate gyrus via the perforant pathway. Both anatomic and neurophysiologic investigations are proposed to continue to examine these modulatory influences. In addition, newly established techniques will be used to evaluate the responsiveness of the dentate gyrus synaptic pathways in the freely behaving animal during acute and chronic opioid administration in order to determine the functional significance of endogenous opioid substances in opiate tolerant and nontolerant animals.